Emulsion and Suspension Stability Flashcards
What is a colloid?
A disperse system in which one phase is in the form of tiny particles or droplets
Why are dispersed systems used for hydrophobic drugs?
- Cannot be dissolved in water
- Dissolved in oil instead
- Oil is dispersed in water (isotonic) to form an emulsion
What stabilises emulsions?
Polymer/surfactant sits at interphase e.g. molecular film on oil droplets
How large are droplets in emulsions?
From 10μm for coarse systems to less than 200nm for fine emulsions
What process does an emulsifier stop?
- The re-separation of oil and water to OG low energy system
- Emulsion requires large amount of energy to create large amount of new surface; dispersed emulsion has a higher energy than unmixed oil and water so will revert back
How do emulsions keep droplets apart?
The surfactant (emulsifier) forms a charged layer around the droplet at the interphase; repulsion of similar charges yields a stable emulsion
What applications are there for emulsions?
Intravenous:
- Total Parenteral Nutrition; administration of fats as intralipid, feeding emulsion simulates chylomicrons
- Delivery of hydrophobic drugs
Oral:
- Fats; enteric feeds
- Delivery of hydrophobic drugs
Intramuscular:
- W/O emulsions for sustained release
- Emulsion vaccine adjuvants
What excipients are acceptable for emulsion use?
IV:
- Oil phase; soya bean oil/medium chain triglyceridies
Emulsifiers:
- Phospholipids (must be purified; some components toxic e.g. phosphatidylinositol) from egg yolk or soya beans
- Hydrophilic Pluronics (non-ionic surfactants)
- Polysorbate/bile salts in small volume parentals
IM:
- Sesame oil
- Squalane and Pluronic L121 in Syntex Adjuvant Formulation (designed to induce immune response)
How are hydrophobic oil-soluble drugs incorporated into emulsions?
Dissolved in oil which is then emulsified; drug must be v. hydrophobic (Log P > 5) or drug will transfer through aqueous phase and crystallise out
What are surface active drugs and how can they be incorporated?
- One part hydrophilic, one part hydrophilic
- Absorbed at the interphase
What happens in flocculation? What does it mean for the disperse system?
- Particles/droplets cluster together in an open structure
- They maintain their individual identity though
- Can be redispersed to single particles/droplets by shaking
What is coagulation/aggregation and what does this mean for the disperse system?
- Small aggregates form
- Surface area is decreased so surface tension is experienced by fewer molecules
- Attractive forces between particles very strong
- Cannot be redispersed to single particles by shaking; permanent failure of medicine
What is coalescence and what are its consequences for a disperse system?
- ‘Sedimentation’
- Droplet structure lost entirely
- Impossible to reform emulsion
- Total failure
- AKA ‘cracking’
What forces are acting on particles in disperse systems?
- Particles of less than 2 microns diameter are constantly moving due to Brownian motion
- Kinetic energy depends on temperature and shaking etc.
- Particles experience repulsion due to electrostatic interactions
- Particles also experience attraction due to vdWs
- Steric forces exhibited if they have a non-ionic surfactant coating them (steric hindrance)
What is the DVLO theory?
Theory of balance between electrostatic repulsion and attractive forces.
What does the attractive force/vdW (Va) between particles depend on?
- Particle radius
- Particle separation (distance between)
What is the relationship between attractive force and particle separation (as per potential diagram)?
- Small attractive force exists at big separations
- Very sharp increase in attraction at small separations
How is charge distributed around a particle in a colloid in relation to repulsive force?
- Most colloidal particles charged (from ion dissolution/ion adsorption via surfactants)
- Electrical double layer formed at surface of colloidal particle; Stern layer and Gouy-Chapmanlayer
- Only so many oppositely charged ions occupy the colloidal layer; repelling like charges
What is the stern potential?
Potential of absorbed cations on the surface
What is the zeta potential?
Potential at the end of the stern plane
What is the relationship between repulsive force and particle separation (as per potential diagram)?
- Repulsion falls to zero at certain distance quite rapidly; where there still is a weak attractive force
- Repulsion does not increase sharply at close separations
What is happening in a disperse system at the Secondary Minimum?
- Weak attraction
- Causes flocculation (even at large separation distances)
What is happening in a disperse system at the Primary Maximum?
- Repulsive barrier to aggregation; repulsion between particles not present until quite close together
- Results in colloidal stability
What is happening in a disperse system at the Primary Minimum?
- Permanent aggregation of particles
- Energy has superseded Primary Maximum overcoming repulsor forces
Where does low kinetic energy place a particle in terms of a potential diagram, and what is the end result?
- Primary Maximum too great a barrier
- Particle has insufficient energy to continue its path towards neighbouring particle
- Particle also has insufficient energy to escape the Secondary Minimum
RESULT - FLOCCULATION
Where does intermediate kinetic energy place a particle in terms of a potential diagram, and what is the end result?
- Primary Maximum too great a barrier
- Particle has insufficient energy to continue its path towards a neighbouring particle
- Particle escapes the Secondary Minimum (Brownian Motion)
RESULT - STABLE COLLOIDAL FORMULATION
Where does high kinetic energy place a particle in terms of a potential diagram, and what is the end result?
- Primary Maximum is insufficient to stop particle
RESULT - COAGULATION
